J Tissue Eng Regen Med. 2017 Jun 28. doi: 10.1002/term.2507. [Epub ahead of print]

Bone marrow-on-a-chip: Long-term culture of human hematopoietic stem cells in a 3D microfluidic environment.

Sieber S^1,2, Wirth L¹, Cavak N¹, Koenigsmark M¹, Marx U³, Lauster R¹, Rosowski M¹.

Abstract

Multipotent hematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to this date no in vitro model exists that truthfully mimics the aspects of the bone marrow niche and simultaneously allows the long-term culture of HSPCs. In this study, we present a novel 3D co-culture model, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells (MSCs) and cord blood derived HSPCs, enabling successful HSPC culture for a time span of 28 days within the microfluidic Multi-Organ-Chip (MOC). The HSPCs were found to stay in their primitive state (CD34⁺ CD38^- ) and capable of GEMM colony formation. Furthermore, a microenvironment was formed bearing molecular and structural similarity to the in vivo bone marrow niche containing ECM and signaling molecules known to play an important role in HSPC homeostasis. Here, we present for the first time a novel human in vitro bone marrow model, capable of long-term culture of primitive HSPCs in a microfluidic environment. This article is protected by copyright. All rights reserved.